An Unusual Case of Lethal Strongyloides stercoralis-Associated Chronic Fulminant Colitis in an Immunocompetent Patient

A 70-year-old immunocompetent Lebanese male presented with 3-month history of watery diarrhoea and abdominal pain after recently arriving to Australia from Lebanon. He had a colectomy for an iatrogenic bowel perforation associated with a colonoscopy in Lebanon several months prior. His computed tomography (CT) scan demonstrated pancolitis. Stool culture and polymerase chain reaction (PCR) were positive for Strongyloides stercoralis. Despite Strongyloides treatment and total parenteral nutrition, his pancolitis unexpectedly persisted despite negative stool cultures, and the patient failed to progress over several weeks with worsening abdominal pain. A colectomy was considered. However, due to his recent myocardial infarct requiring cardiac stenting, his anticoagulant and antiplatelets could not be ceased for at least 3 months without significant cardiac risk. After hospitalisation for several weeks in Australia, he was discharged against medical advice and flew back to Lebanon, where he presented with worsening pain and underwent a subtotal colectomy. Unfortunately, he developed multiorgan failure and died 3 weeks following his colectomy. Strongyloides-related pancolitis is a rare condition in immunocompetent adults that has the potential to persist and be lethal, despite microbiological antiparasitic eradication.


Introduction
Strongyloides stercoralis is an intestinal nematode estimated to infect over 600 million people worldwide, mostly in tropical and subtropical areas [1].Parasitic adult females reside in the duodenum or stomach and produce eggs that hatch in the mucosa [2].After a series of moults, larvae either progress through an autoinfective pathway, where they penetrate the wall of the large intestine or skin to reinfect the host, or larvae are passed into the environment through faeces, where other hosts can be infected [2,3].Due to the capacity for autoinfection, strongyloidiasis can persist for decades in people who have migrated from endemic areas.
Chronic infection may be asymptomatic or be associated with dermatological, respiratory, or gastrointestinal symptoms, with colitis in an immunocompetent host being rarely described [2,4].In immunocompromised hosts, there is a shift in host-parasite balance, with an accelerated autoinfection, and large numbers of larvae disseminating through the tissues of the body with a high mortality [5].Here, we present an unusual case of persistent pancolitis in an immunocompetent patient, associated with strongyloidiasis that was unresponsive to antiparasitic therapy, with pancolitis subsequently complicated by perforated diverticulosis.
1.1.History.A 70-year-old Middle Eastern male presented to the emergency department with a three-month history of diarrhoea, vomiting, abdominal distention, and generalised abdominal discomfort.Tis was associated with 17 kilograms of unintentional weight loss.Several months prior to this presentation, while he was in Lebanon, he had an iatrogenic perforation of the sigmoid colon during a colonoscopy for investigation of per-rectal bleeding requiring an emergency laparotomy and a segmental colectomy with covering ileostomy which was reversed three months later.Five months after reversal, he developed diarrhoea, vomiting, and abdominal pain and was readmitted to hospital.During this admission, he developed a myocardial infarction which required a coronary angiogram and placement of a drug-eluting stent.He had a history of atrial fbrillation, hypertension, dyslipidaemia, and gastrointestinal refux disease.His regular medications included aspirin, clopidogrel, and apixaban.Tere was no history of corticosteroid usage nor other immunosuppressant agents.He did not have any personal or family history of colorectal cancer nor infammatory bowel disease (IBD).He was a current smoker with a 20-pack-year history.Tere was no history of travel to other areas endemic for strongyloidiasis, such as Asia and the Pacifc, sub-Saharan Africa, and Latin America/Caribbean, nor contact with individuals with known Strongyloides infection.He left Lebanon, as he was concerned he was deteriorating, and few to Australia, where he presented to the emergency department on arrival.

Physical Examination.
His vital signs were normal.Te abdomen was distended, soft with mild generalised tenderness without peritonism.Tere was a palpable mass in the left midabdomen but no clinical features of peritonitis.Digital rectal examination was unremarkable.Tere were no skin rashes.Tere were no pulmonary infltrates on the chest X-ray.
Stool agar plate culture was positive with a moderate level of larvae present and Strongyloides stercoralis were identifed on microscopy.Tere was no evidence of Clostridioides difcile in the stool.Strongyloides species were also confrmed on stool polymerase chain reaction (PCR) (see Appendix 1 for details of primers and probes used) [6], and there was no peripheral blood eosinophilia.Blood cultures were also positive for carbapenemase-producing Escherichia coli (CPE) and the presence of a New Delhi metallo-β-lactamase (NDM) gene was confrmed on PCR.Te infectious diseases team was consulted, and he was initially commenced on two days of ivermectin 18 mg daily orally for Strongyloides treatment.For the management of the CPE bacteraemia and colitis, he was commenced on amikacin 1750 mg daily intravenously for 2 weeks, trimethoprim/sulfamethoxazole 160 mg/800 mg twice daily intravenously for 3 weeks, and metronidazole 500 mg twice daily intravenously for 3 weeks.He was unable to tolerate oral intake and commenced on total parenteral nutrition.

Patient Progress after Initial Investigations.
Although the patient demonstrated some initial clinical improvement with the above regimen, his clinical progress plateaued with intermittent fevers, a persistent leucocytosis, and a CRP between 80 and 130 mg/L.His electrolytes, renal function, and albumin slowly improved with total parenteral nutrition within 5 weeks.A repeat abdominopelvic CT scan three weeks postadmission demonstrated worsening pancolitis, without features of ischaemia, nor colonic perforation.Ivermectin was restarted one week after discontinuation at 18 mg daily orally, as well as albendazole 400 mg twice daily orally over 2 weeks.
With a failure to progress and worsening colitis on a CT scan, a total abdominal colectomy was considered.However, due to his recent myocardial infarction, the cardiologist advice was that he should not stop his antiplatelet/anticoagulant therapy for at least 3 months.He was referred to the high-risk clinic, and his perioperative mortality was calculated by the perioperative anaesthetist and estimated at 47.6% as per American College of Surgeons Surgical Risk Calculator [7].
A colonoscopy demonstrated ulceration and oedema of the left colon with an infammatory stricture that was able to be traversed (Figure 2).Tere was sparse mild infammation in the right colon and diverticular disease.Biopsies of the colonic stricture demonstrated mild eosinophilia within the lamina propria, without granulomas to suggest IBD (Figure 3).Patchy infammation of the right colon was noted; however, random biopsies of the ascending and transverse colon were unremarkable.Te terminal ileum was unremarkable.Biopsies for cytomegalovirus (CMV) were negative on immunohistochemistry.
To assess for other diferential diagnoses of fulminant colitis, investigations for ischaemic colitis, autoimmune diseases, vasculitis, CD3 absolute counts, tuberculosis, 2 Case Reports in Infectious Diseases  Case Reports in Infectious Diseases At the eleventh week of admission, the patient was still unable to tolerate oral intake due to pain, nausea, and vomiting.He was never considered to have immunosuppressive therapy due to concerns of Strongyloides stercoralis hyperinfection, and there was no evidence of infammatory bowel disease.Te patient was consented for surgery and explained that he had approximately 40% risk of death.Te patient decided to discharge against medical advice.Te patient's family was contacted postdischarge against medical advice and we were informed that he had fown back to Lebanon and approximately 1 week after discharge he presented to a hospital in Lebanon with worsening abdominal pains.No endoscopies were performed.A decision was made by the surgeons in Lebanon to perform a subtotal colectomy a few days later.
Te histopathology demonstrated a 90 cm segment of large bowel with pancolonic congestive colonic wall, hypertrophy of the muscularis propria, thickened mesocolon, and several diverticulae which were perforated, with several mesocolic abscesses.No Strongyloides was seen nor any features of IBD.Te patient remained in the intensive care unit postoperatively, developed multiorgan failure, and died approximately 3 weeks after surgery.
A summary of the clinical progress, laboratory fndings, and treatments is provided in Table 1.

Discussion
S. stercoralis infection is generally considered in immunosuppressed patients or if there is a history of probable exposure in an endemic area, regardless of elapsed time since exposure [8].It is symptomatic in 50% of cases, most often manifesting with gastrointestinal symptoms such as nausea, diarrhoea, haematochezia, and difuse abdominal pains [9].In immunocompromised patients, it may lead to colitis and hyperinfection syndrome characterised by disseminated Strongyloides, with mortality as high as 87% [10].
Tere have been other rare case reports of chronic colitis in immunocompetent patients associated with Strongyloides, but none that persisted after microbiological eradication following antiparasitic activity.Berry et al. reported an immune-competent 16-year-old woman who underwent fve colonic operations over fve years after a delayed diagnosis of life-threatening chronic haemorrhagic Strongyloides colitis [4].Tey suggested that the larvae invaded the mucosal walls of the colon at repeated intervals which may be induced by conditions which delay elimination of faecal contents, such as diverticulosis (as was seen in our patient) [4].Recurrent S. stercoralis colitis was reported in a 75year-old man, 14 months after initial treatment, negative surveillance testing, and subsequent resumption of chemotherapy for his multiple myeloma [11].In addition, chronic strongyloidiasis may also manifest with paralytic ileus, as reported in a 70-year-old man with 5 months history of recurrent ileus, with resolution of symptoms after ivermectin [12].
In our patient, there was initial strong laboratory evidence of Strongyloides-related pancolitis, and the persistence of the colitis after eradication with antiparasitic therapy may be related to the presence of parasite antigen.We propose that a putative mechanism may be related to the persistence of dead parasite antigen without the immune modulatory efects of the live larvae [13].Serum eosinophilia has not been shown to be an accurate marker for strongyloidiasis, as was the case in our patient, with only 25% of patients with Strongyloides infection having raised eosinophil count in a retrospective study [14].Routine stool examination identifes up to 30% of cases due to low infectious burden and intermittent larval excretion; thus, repeat stool samples are advised to improve the sensitivity of the test [15].
Strongyloides colitis on colonoscopy may demonstrate yellowish-white nodules, mucosal erosions, erythema, submucosal haemorrhage, and ulcerations which may alternate between portions of normal mucosa [16,17].Our patient had some of these features with appearances that are similar to IBD, including patchy infammation afecting mostly the left and to a lesser extent, the right colon.Macroscopically, the colitis may be indistinguishable between S. stercoralis infection and IBD, leading to misdiagnosis.In our patient, IBD was ruled out from histopathology.Tis distinction is important, as three case reports misidentifed Strongyloides colitis by initially treating a patient with immunosuppressive therapy on a presumptive diagnosis of IBD, leading to hyperinfection, severe sepsis, and death [18][19][20].
Although prohibitive in this patient, an earlier total abdominal colectomy may have avoided his demise.We have illustrated that if persistent Strongyloides-related chronic colitis was left untreated without a radical approach, the natural history was lethal from worsening infammation, colonic perforation, and sepsis.
Te limitations of this case report need to be outlined.Firstly, we are assuming that his persistent pancolitis is directly related to his earlier laboratory diagnosis of Strongyloides related colitis, perhaps due to persistence of dead parasite antigen in the colon.A complete biochemical, microbiological, radiological, and histopathological analysis had returned negative for infections, infammatory, autoimmune, or vascular causes for persistent pancolitis.Secondly, although every attempt was made to retrieve his medical records from Lebanon, we were unable to clearly obtain details on what type of colectomy he had and specifcally what led to his multiorgan failure and death postoperatively.

Conclusion
We report a rare case of lethal Strongyloides stercoralis-related pancolitis in an immunocompetent male with no signifcant risk factors.Although there was microbiological evidence of clearance with antiparasitic therapy, there was unexpected persistence of colitis.We propose a putative mechanism for the chronic colitis, related to ongoing colonic infammation from persistence of dead parasite antigen, without the immune modulatory efects of the live larvae.Although it was prohibitive for this patient, earlier surgery may have prevented death from persistent pancolitis.

Figure 1 :Figure 2 :
Figure 1: Abdominopelvic CT scans (axial and coronal views) demonstrating pancolitis (blue arrow) with a stricture in the mid-descending colon (white arrowhead) and dilated large bowel loops proximally.

Table 1 :
Summary of the clinical, laboratory fndings, and treatment.

Table 1 :
Continued.Case Reports in Infectious Diseases microsporidia, and hepatitis screens were performed.All these tests were negative.After the antiparasitic therapy, repeat stool culture for Strongyloides and PCR were negative.